Brinkhorst was an undersecretary of state of foreign affairs and a minister of agriculture. Furthermore he was the leader of the D66-group in the Second Chamber of the Dutch parliament. He was also a minister of economic affairs in the second Balkenende cabinet.
Journalists gave him the nickname Brilly the kid.

From 1962, and from 1965 as a director, he worked at the Europe-institute at the Rijksuniversiteit Leiden where he became a Reader (Lector) in 1965 as well. During the period 1967-1973 he was Professor of European Law at the University of Groningen (Rijksuniversiteit Groningen in Dutch). On
11 May 1973 he became Deputy Minister of Foreign Affairs in the Cabinet of Den Uyl.

Staatssecretaris Brinkhorst talks with the second chamber members of his party during the cabinets formation of 1977.

In 1977 he was again a member of the Second Chamber of the Dutch parliament for D66 and in 1981 became the leader of his party in parliament. From 1983-1987 he was Ambassador of the European Community in Japan.

Brinkhorst was also a member of the Provinciale Staten (the provincial parliament) of the province of Groningen for D66, a member of the board of advice of the World Resources Institute in Washington DC, a member of the board of governors of the Nederlands Economisch Instituut (Dutch Economical Institute), a professor by special appointment of international environmental law at the University of Leiden, a member of the Board of Directors of the Salzburg Seminar, a member of the Board of Directors of the International Institute of Sustainable Development, and a professor (on a temporary basis) of international environmental law at the University of Lausanne.

On 8 June 1999 he became the minister of agriculture, environmental control and fishery in the cabinet Kok-II. Afterwards (2002) he became an Adviser of European Affairs at NautaDulith in Brussels and was awarded a professorship in transnational and European Governance at the University of Tilburg.
After the electoral defeat of D66 he became a minister of economic affairs in the second Balkenende cabinet. Brinkhorst, as well as Alexander Pechtold, resigned from his minister post after the second Balkenende cabinet lost the confidence of parliament on 29 June 2006. The next day, Balkenende offered the resignation of the full cabinet to the Dutch Queen.